release of glucocorticoids from the adrenal cortex. Cortisol is the main glucocorticoid in

humans and corticosterone (CORT) is the main glucocorticoid in rats. The elevated

circulating levels of glucocorticoids decrease the further activity of the HPA axis through

exertion of negative feedback on neurosecretory cells of the hypothalamus and

corticotrope cells of the pituitary (for review, see Whitnall, 1993).

 Altered regulation of hormonal activity in depressed patients is thought to be a

result of increased activity of specific CRH-containing neurons in the PVN. The average

total number of such neurons is up to four times higher in depressed patients when

compared to normal control subjects. Also, co-localization of AVP in CRH-expressing

neurons has been indicated as an index for stress-activated neuronal activity. The

average number of neurons co-expressing both CRH and AVP in depressed patients is up

to three times higher than those for normal subj ects. These results suggest that increased

expression of CRH- and AVP-containing neurons in the PVN may cause at least a

fraction of the collective symptomatology of depression (Raadsheer et al., 1994).

 When physically or emotionally stressed, non-human animals endure physiological

responses that lead to behavioral and hormonal impairment which may be fundamentally

similar to the impairment seen in human stress-induced psychopathology. Behavioral

responses to stressful stimuli (including increased drug-taking propensity, decreased

performance in learning tasks, sleep disturbances, and unsocial behavior) have been

observed in a variety of species (for review, see Amiel-Tison et al., 2004). Also, there is

significant evolutionary homology in stress-regulating peptides, such as CRH and CRH-

related molecules (Chang and Hsu, 2004). Thus, the use of an animal model for